Signal transmission from the mechanical forces to the various intracellular activities is a fundamental process during tissue development. Despite their critical role, the mechanism of mechanical ...forces in the biological process is poorly understood. In this study, we demonstrated that in the response to hydrostatic pressure (HP), the piezo type mechanosensitive ion channel component 1 (PIEZO1) is a primary mechanosensing receptor for odontoblast differentiation through coordination of the WNT expression and ciliogenesis. In stem cells from human exfoliated deciduous teeth (SHED), HP significantly promoted calcium deposition as well as the expression of odontogenic marker genes, PANX3 and DSPP, and WNT related-genes including WNT5b and WNT16, whereas HP inhibited cell proliferation and enhanced primary cilia expression. WNT signaling inhibitor XAV939 and primary cilia inhibitor chloral hydrate blocked the HP-induced calcium deposition. The PIEZO1 activator Yoda1 inhibited cell proliferation but induced ciliogenesis and WNT16 expression. Interestingly, HP and Yoda1 promoted nuclear translocation of RUNX2, whereas siRNA-mediated silencing of PIEZO1 decreased HP-induced nuclear translocation of RUNX2. Taken together, these results suggest that PIEZO1 functions as a mechanotransducer that connects HP signal to the intracellular signalings during odontoblast differentiation.
Cell‐ and tissue‐specific extracellular matrix (ECM) composition plays an important role in organ development, including teeth, by regulating cell behaviors, such as cell proliferation and ...differentiation. Here, we demonstrate for the first time that von Willebrand factor D and epidermal growth factor (EGF) domains (Vwde), a previously uncharacterized ECM protein, is specifically expressed in teeth and regulates cell proliferation and differentiation in inner enamel epithelial cells (IEEs) and enamel formation. We identified the Vwde as a novel ECM protein through bioinformatics using the NCBI expressed sequence tag database for mice. Vwde complementary DNA encodes 1773 amino acids containing a signal peptide, a von Willebrand factor type D domain, and tandem calcium‐binding EGF‐like domains. Real‐time polymerase chain reaction demonstrated that Vwde is highly expressed in tooth tissue but not in other tissues including the brain, lung, heart, liver, kidney, and bone. In situ hybridization revealed that the IEEs expressed Vwde messenger RNA in developing teeth. Immunostaining showed that VWDE was localized at the proximal and the distal ends of the pericellular regions of the IEEs. Vwde was induced during the differentiation of mouse dental epithelium‐derived M3H1 cells. Vwde‐transfected M3H1 cells secreted VWDE protein into the culture medium and inhibited cell proliferation, whereas ameloblastic differentiation was promoted. Furthermore, Vwde increased the phosphorylation of extracellular signal‐regulated kinase 1/2 and protein kinase B and strongly induced the expression of the intercellular junction protein, N‐cadherin (Ncad). Interestingly, the suppression of endogenous Vwde inhibited the expression of Ncad. Finally, we created Vwde‐knockout mice using the CRISPR‐Cas9 system. Vwde‐null mice showed low mineral density, rough surface, and cracks in the enamel, indicating the enamel hypoplasia phenotype. Our findings suggest that Vwde assembling the matrix underneath the IEEs is essential for Ncad expression and enamel formation.
von Willebrand factor D and epidermal growth factor domains, a previously uncharacterized extracellular matrix protein, are specifically expressed in teeth and regulate cell proliferation and differentiation in inner enamel epithelial cells and enamel formation.
The causes of premature loss of deciduous teeth have been reported to be associated with caries, periodontal disease, trauma, occlusal trauma, bruxism, and systemic diseases. However, in daily ...clinical practice, there are rare cases in which it is difficult to identify the cause of premature loss. Here, we report a case of premature loss of a deciduous canine in a 4-year and 6-month-old boy.The patient was referred to our clinic with premature loss of the mandibular left deciduous canine. As the intraoral findings, the mandibular left deciduous canine tooth had fallen out, and the dropout cavity was observed. He had tooth attrition caused by bruxism, but no dental history of caries or trauma was noted. To begin with, a blood test was performed for screening of systemic diseases. In addition, bacteriological examination was performed to evaluate the association with periodontopathic bacteria. However, there were no abnormal findings in those examinations. Next, we carefully observed the fallenout tooth. Although there was no abnormal appearance on visual inspection, fracture lines with a crack degree were found under stereoscopic microscope observation. Furthermore, CT examination revealed that the fracture continued from the crown surface to the pulp cavity. Finally, excessive physical irritation caused by bruxism had resulted in crown fracture, which might induce pulp necrosis and apical periodontitis. Furthermore, excessive occlusal pressure due to the bruxism and lateral movement would affect this condition. Because primary teeth have less mature calcification than permanent teeth and due to their structural characteristics, tooth microcracks often occur. Furthermore, excessive occlusal force applied to the tooth due to trauma or bruxism may cause microcracks, which may lead to unexpected crown fractures and premature loss of teeth.
The regulation of the mesenchymal stem cell (MSC) programming mechanism promises great success in regenerative medicine. Tissue regeneration has been associated not only with the differentiation of ...MSCs, but also with the microenvironment of the stem cell niche that involves various cytokines and immune cells in the tissue regeneration site. In the present study, fibroblast growth factor 2 (FGF2), the principal growth factor for tooth development, dental pulp homeostasis and dentin repair, was reported to affect the expression of cytokines in human dental pulp-derived MSCs. FGF2 significantly inhibited the expression of chemokine C-C motif ligand 11 (CCL11) in a time- and dose-dependent manner in the SDP11 human dental pulp-derived MSC line. This inhibition was diminished following treatment with the AZD4547 FGF receptor (FGFR) inhibitor, indicating that FGF2 negatively regulated the expression of CCL11 in SDP11 cells. Furthermore, FGF2 activated the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinases (JNK) in SDP11 cells. The mechanism of the FGFR-downstream signaling pathway was then studied using the SB203580, U0126 and SP600125 inhibitors for p38 MAPK, ERK1/2, and JNK, respectively. Interestingly, only treatment with SP600125 blocked the FGF2-mediated suppression of CCL11. The present results suggested that FGF2 regulated the expression of cytokines and suppressed the expression of CCL11 via the JNK signaling pathway in human dental pulp-derived MSCs. The present findings could provide important insights into the association of FGF2 and CCL11 in dental tissue regeneration therapy. Key words: dental pulp-derived mesenchymal stem cells, fibroblast growth factor 2, fibroblast growth factor receptor signal, C-C motif ligand 11, c-Jun N-terminal kinase
A Tick Bite on the Palate: A Case Report Kurogoushi, Rika; Iwata, Kokoro; Kitamura, Takamasa ...
The Japanese Journal of Pediatric Dentistry,
2020/11/25, Letnik:
58, Številka:
3
Journal Article
There have been reports of tick bites in the maxillofacial region, but no reports in the oral cavity. Here we report a case of a tick bite on the palate. The patient was a boy aged 1 year and 0 ...months. An elastic hard tumor with a smooth surface, black partly brown mottled pattern, and well-defined border was observed at the center of the right side of the palate. On the evening of the first visit to our clinic, he exhibited a fever ranging from 39.1 to 39.6℃ and exanthema on the buttocks, palms and soles. A nearby pediatrician diagnosed it as hand, foot and mouth disease and prescribed cephem antibiotics to prevent secondary infection. Six days later, the fever temporarily subsided. Two days later, the fever recurred and exanthema was observed. Then, his fever subsided suddenly. Ten days after the first visit to our department, the tumor disappeared, and several 1- to 2-mm indentations were found at the site where the tumor was located, and there were bullae around it. Three months later, the bullae disappeared. Nine months later, the patient made steady progress.There are many infectious diseases transmitted by ticks which may become fatal if they become severe. Tick bites rarely occur inside the mouth, but this can happen at an early age when very young children tend to put anything into their mouths.
The characteristics of disabilities and illnesses are gradually being understood end the social environment and welfare system for them are improving. However, the environment of dental care at the ...dental clinic for the children with disabilities and illnesses is not yet sufficient, and urgent environmental improvement is required. Therefore, to clarify the problems of dental situation for those patients, we investigated first-visit patients with disabilities and illness who visited our department from 2013 to 2018. Of the 1,301 first-visit patients, the percentage of children with disabilities and illnesses was 49%. In this study, the disabilities and illnesses were categorized with physical disabilities, sensory disorders, internal disorders, developmental disorders, seizure disorders, congenital malformations, chromosomal abnormalities, and genetic abnormalities. The 323 patients included 4% with physical disabilities, 11% with sensory disorders, 15% with internal disorders, 34% with developmental disorders, 8% with seizure disorders, 14% with congenital malformations, 8% with chromosomal abnormalities, and 6% with genetic abnormalities were further investigated. Caries was the most common complaint (31%) followed by cleft lip and palate (17%), dental check-up (14%), surgical treatment (11%), denture guidance (8%), trauma (4%), and swallowing (3%). Ninety-three percent of the patients brought a letter of referral and 7% did not. The number of patients by residential area was highest in Tokushima City (37%), where our hospital is located. This was followed by Anan City (10%) and Naruto City (8%). Nine percent of the patients came from outside Tokushima Prefecture. The dental needs of children with disabilities and illness, as well as the environment and system surrounding them, should be analyzed from the standpoint of both the patient and the medical personnel, so that the needs of both parties can be met.
The Heisei Era ended at the end of April 2019 and the Reiwa Era began.For about 30 years in the Heisei era after the Showa era, the environment surrounding children changed rapidly, including the ...economic downturn, the acceleration of late marriage and declining birthrate, and progress in information and communication technology. As a result, individual households have diversified and a large polarization has become apparent. As pediatric dentists, we need to deal with and support children with all kinds of problems. Therefore, to clarify the transition of the first-visit patients in our clinic, we categorized the 30 years from 1989 to 2018 by five-year groups: early (1989-1993), middle (1997-2001) and late (2013-2018) stages, with a total of 5,892 patients, and then investigated and analyzed their properties. As a result, the number of new patients decreased from 2,477 in the early stage to 1,301 in the late stage. The male-female ratio was approximately 1:1 in each period. As for age, school age was the highest at about 40%, and there was no significant change in the age composition in each period. The most common chief complaint during each period was tooth decay, but it decreased from 44% in the early stage to 27% in the late stage. The proportion of children who brought a letter of referral increased from 23% in the early stage to 83% in the late stage, and the proportion of children with disabilities and illness increased from 13.8% in the early stage to 33% in the late stage. Compared to the early days, the chief complaints have diversified, and it has become clear that the functional differentiation of general dental clinics and university hospitals is progressing. Furthermore, it was suggested that the importance of medical and dental cooperation will increase in the future.
A sports-related dental injury is defined as injuries to the oral and maxillofacial regions associated with sports activities, and involves tooth fracture and luxation, facial bone and ...temporomandibular fractures, and soft tissue injury. Participants in sports activities are always at risk for traumatic injury, with the oral and maxillofacial region often affected. Dental injuries also have a high rate of occurrence among sports-related injuries received during school physical education classes and club activities. Unfortunately, nearly all such dental injuries are irreversible, and the loss of teeth or their supporting tissues has a significant impact on the quality of life of affected individuals. Thus, for prevention of sports-related dental injuries, it is important for dental professionals to disseminate correct knowledge regarding oral health, as well as provide information to reduce and treat risk factors such as dental caries, periodontal disease, and occlusal problems. In particular, use of mouthguard is one of the most effective ways to prevent sports-related dental injuries that occur in sports and physical activity participants. Recently, along with increased health consciousness, the number of individuals who participate in sports and fitness activities is also increasing. Outside of the bounds of conventional dental clinical treatment, dentists are encouraged to actively be involved in local and regional organizations related to sports, recreation, and physical activity opportunities, in order to contribute to promotion of safety and health, including injury prevention. In this review, we discuss various findings to prevention of sports-related dental injuries in children.
Cells sense and respond to extracellular mechanical stress through mechanotransduction receptors and ion channels, which regulate cellular behaviors such as cell proliferation and differentiation. ...Among them, PIEZO1, piezo-type mechanosensitive ion channel component 1, has recently been highlighted as a mechanosensitive ion channel in various cell types including mesenchymal stem cells. We previously reported that PIEZO1 is essential for ERK1/2 phosphorylation and osteoblast differentiation in bone marrow-derived mesenchymal stem cells (BMSCs), induced by hydrostatic pressure loading and treatment with the PIEZO1-specific activator Yoda1. However, the molecular mechanism underlying how PIEZO1 induces mechanotransduction remains unclear. In this study, we investigated that the role of the C-terminus in regulating extracellular Ca2+ influx and activating the ERK1/2 signaling pathway. We observed the activation of Fluo-4 AM in the Yoda1-stimulated human BMSC line UE7T-13, but not in a calcium-depleted cell culture medium. Similarly, Western blotting analysis revealed that Yoda1 treatment induced ERK1/2 phosphorylation, but this induction was not observed in calcium-depleted cell culture medium. To investigate the functional role of the C-terminus of PIEZO1, we generated HEK293 cells stably expressing the full-length mouse PIEZO1 (PIEZO1-FL) and a deletion-type PIEZO1 lacking the C-terminal intracellular region containing the R-Ras-binding domain (PIEZO1-ΔR-Ras). We found that Yoda1 treatment predominantly activated Flou-4 AM and ERK1/2 in PIEZO1-FL-trasfected cells but neither in PIEZO1-ΔR-Ras-transfected cells nor control cells. Our results indicate that the C-terminus of PIEZO1, which contains the R-Ras binding domain, plays an essential role in Ca2+ influx and activation of the ERK1/2 signaling pathway, suggesting that this domain is crucial for the mechanotransduction of osteoblastic differentiation in BMSCs.
•Ca2+ influx is necessary for the phosphorylation of ERK1/2 via PIEZO1 activation in BMSCs.•The C-terminus containing the R-Ras-binding region of PIEZO1 plays a role in Ca2+ influx.•PIEZO1 activates the ERK1/2 signaling pathway which requires the R-Ras-binding domain at the C-terminus of PIEZO1.
Cover Image, Volume 237, Number 3, March 2022 Iwata, Kokoro; Kawarabayashi, Keita; Yoshizaki, Keigo ...
Journal of Cellular Physiology,
March 2022, 2022-03-00, Letnik:
237, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Front Cover: The cover image is based on the Research Aritcle von Willebrand factor D and EGF domains regulate ameloblast differentiation and enamel formation by Tsutomu Iwamoto et al., ...https://doi.org/10.1002/jcp.30667.
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